ETHANOL SUBSTITUTES

Abstract: A composition providing the physiologic sensations of ethanol, comprising an alkoxy glycol ether and preferably further comprising a cooling agent and an oral care or pharmaceutical active.

Description: ETHANOL SUBSTTTUTES TECHNICAL FIELD The present invention relates to compositions which provide the physiologi sensations of ethanol and which are suitable for use in, e.g., π-outhrinse, pharmaceu tical, or topical preparations. B CKGROUND OF THE INVENTION Ethanol is a choice ingredient, inter alia, in view of its solvent, astringent, an antiseptic properties for use in foods, pharmaceuticals or chemicals and, therefore, i of invaluable worth to the industrial community. While most of the ethanol produced worldwide is used in the manufacture o various alcoholic beverages, as already suggested, ethanol is quite popular amongs the scientific and industrial communities as well. Used systemically, ethanol is a no table CNS depressant. In its denatured form, ethanol is used externally as an anti septic, rubifacient and/or astringent. Similarly, industrial chemists use ethanol, prin cipally in its denatured form, for its solvent properties or as an industrial fuel. Another important reason for ethanol's continued importance as an industrial ingredient stems from its use in topical preparations and relates to the sensory at- tributes associated with its efficacy. These attributes are most commonly experi¬ enced when ethanol is used in the form of a rubbing alcohol, a mouthrinse, or cough syrup. The primary sensory attributes ascribed to ethanol may be described with respect to the perceived location of the sensation. Topical sensations experi¬ enced, e.g., in the oral cavity (or upon skin) include those described as a bite/burn(ing), numbness, and tingling type of sensation while those shared by the nasal cavity are perceived as a sweet, aromatic, and cooling type of sensation. Considering the commercial importance of compositions which tend to signal efficacy (actual and/or perceived), the advantages to developing compositions which add such a commercially appealing dimension become obvious. The present inventors have unexpectedly discovered such a composition. Specifically, they have discovered a composition comprising a number of distinct compounds combined in such a way so as to provide the sensory attributes of ethanol without actually incorporating ethanol. It is, therefore, an object of the present invention to provide a compositions which provide physiologic sensations similar to ethanol. It is further an object of the present invention to provide an ethanol substitute suitable for use in oral compositions such as mouthrinses, pharmaceutical compositions, and in other topical skin care compositions such as cosmetics, lotions and the like. Still a further objec of the present invention is to provide compositions which when combined wit suitable pharmacologic actives reduce and/or abate plaque, gingivitis, and symptom associated with respiratory disorders, gastrointestinal disorders, and allergies. SUMMARY OF THE INVENTION The present invention relates to a composition which provides physiologi sensations similar to ethanol. The composition comprises: a) an alkoxy or glycol ether, and b) ethyl acetate; in a ratio of alkoxy or glycol ether to ethyl acetate from about 50 to 1 to about 100 to 1. The composition preferably further comprises a cooling agent. The invention still further relates to cosmetic and pharmaceutical composi tions useful in treating, e.g., plaque and/or gingivitis, respiratory disorders, gastrointestinal disorders and allergies; comprising the administration of a safe and effective amount of the compositions of the present invention. All percentages and ratios herein are by weight unless otherwise specified. Additionally, all measurements are made at 25°C unless otherwise specified. By "physiologic sensations" as used herein, include those sensations discerned upon topical administration of ethanol and described as a bite burn(ing), numbness, tingling, and cooling type of mucosal/skin sensation, a sweet, aromatic type of olfac¬ tory sensation, and a bitter/astringent type of taste sensation. By "safe and effective amount," as used herein, is an amount that is effective to mitigate and or treat the symptoms for which the active ingredient is indicated in a human without undue ad¬ verse side effects commensurate with a reasonable risk benefit ratio. DETAILED DESCRIPTION OF THE INVENTION Those components essential and optional to the present invention are de¬ scribed below. Essential Components Alkoxy or Glvcol Ethers Alkoxy or glycol ethers are represented by the general formula: ROCH 2 CR'HOR where R is H-, phenyl group , or an alkyl group of between 1 and 4 carbons and R' is H- or OH-. The alkoxy or glycol ethers useful to the present invention include those ethers formed by alkoxy addition to epoxides. Alkoxy or glycol ethers preferred for use in the present invention are selected from the group consisting of 2- phenoxyethanol, 2-butoxyethanol, 2-ethoxyethanoL, or 2-phenoxypropanol. Moreover, mixtures of these compounds may also be use in the compositions of t present invention. Without being limited to theory, the alkoxy or glycol ethers are believed t provide more of the burn/bite component useful in imitating ethanol's overall effec Alkoxy or glycol ethers are further described in Remington's Pharmaceutical Sc ences, pp. 1313-1314, (Alfonso R Gennaro, editor) (18th ed. 1990) and under repr sentative compounds in Hawley's Condensed Chemical Dictionary, pp. 489-490, 97 (Revised by Richard J. Lewis, Sr.) (12 th ed. 1993), both of which are herein incorp rated by reference. When used in a pharmaceuticcal or skin care composition, the alkoxy glycol ethers are present at a level form about 0.1% to about 5%. Ethyl Acetate Ethyl Acetate, which is represented by the formula: CH3COOC2H5 . is widely used commercially as a flavoring agent. It is also used industrially to pr vide artificial fruit essences and, further, as a solvent for a variety of organic co pounds, particularly nitrocellulose varnishes and lacquers. Without being limited b theory, ethyl acetate is believed to provide more of the aromatic/burn(ing) compo nent useful in imitating ethanol's overall effect. Ethyl Acetate is further described i Hawley's Condensed Chemical Dictionary, pp. 970-971, (Revised by Richard J. Le wis, Sr.) (12 ed. 1993), which is herein incorporated by reference. When used in a pharmaceutical and skin care composition, ethyl acetate i present in the composition at a level from about 25 ppm to about 75 ppm, preferabl within the range from about 30 ppm to about 70 ppm. Optional Components Cooling Agents The present invention may further comprise a cooling agent or a combinatio of cooling agents. Cooling agents are compounds which directly effect those nerv endings responsible for hot or cold sensations. Suitable cooling agents are mentho menthol-based or acyclic carboximides, and menthol-based or acyclic ketals (acetals) The cooling agents particularly preferred for use in the present invention are thos selected from the group consisting of 3-1-menthoxy propane- 1,2-diol, N-substituted p-menthane-3-carboxamides and acyclic carboxamides and mixtures thereof. Whil not to be limited by theory, it is believed that the coolant element of the inventio provides more of the bite, cooling, numbness and tingling component useful in imitat ing ethanol's overall effect. 3-1-menthoxy propane 1,2-diol is fully described in detail in U.S. Paten 4,459,425, issued July 10, 1984 to Amano et. al, incorporated herein by reference i its entirety. This volatile aromatic is commercially available, as TK-10 from Taka sago Perfumery Co., Ltd., Tokyo, Japan. The N-substituted-p-menthane-3-carboxamides are fully described in U.S Patent 4,136,163 to Watson et al., issued January 23, 1979 incorporated herein b reference in its entirety. The most preferred cooling agent of this class is N-ethyl-p menthane-3-carboxamide which is commercially available as WS-3 from Wilkinso Sword Limited. Useful acyclic carboxamides are fully described in U.S. Patent 4,230,688 t Rowsell et al., issued October 28 1980 incorporated herein by reference in its en tirety. The most preferred cooling agent of this class is N,2,3-trimethyl-2-isopropy-- butanamide which is commercially available as WS-23 from Wilkinson Sword Lim ¬ ited. Preferred for use herein is a mixture of 3-1-menthoxy propane 1,2-diol, N- ethyl-p-menthane-3-carboxamide and N,2,3-trimethyl-2-isopropylbutanamide in a ra¬ tio of 1 : 75:42, respectively. These cooling agents are present at a ratio of alkoxy or glycol ether to cooling agent from about 2 to 1 to about 1000 to 1 and when used in a pharmaceutical or skin care composition, at a level of from about 0.01% to about 1%, preferably at from about 0.01% to about 0.4%. Oral Care Actives Oral care actives useful to the present invention include those providing effec¬ tive antiplaque, antibacterial, antitartar, and/or abrasive activity. Suitable antiplaque agents include proteolytic or glycotytic enzymes, nonionic, anionic, or amphoteric surfactants, and various stannous ion salts, are disclosed in U.S. Patent 4.986.981 to Glace et al., U.S. Patent 5.041.236 to Carpenter et al., U.S. Patent 5.180.577 to Polefka et al. and U.S. Patent 5.145.666 to Lukacovic et al., all of which are herein incorporated by reference. Suitable antibacterial agents include the quaternary ammonium salts, bis- biguanide salts, triclosan, thymol, cetylpyridinium, tetradecylpyridinium and hexetid- ine are disclosed in U.S. Patent 5.176.901 to gallopo et al., U.S. Patent 4.656.031 to Lane et al., and U.S. Patent 4.894.220 to Nabi et al., all of which are herein incorporated by reference. Antitartar (or anticalculus) agents are able to complex calcium found in the mixed matrix layers of plaque. This facilitates the loosening of plaque. Suitable anti¬ tartar agents include citric acid/alkali metal citrate combinations along with the van- ous soluble pyrophosphate salts. Pyrophosphates are further described in Kirk Othmer. Encyclopedia of Chemical Technology. 2 nc * ed., vol. 15, Interscience Pub lishers (1968) and in U.S. Patent 5.180.576. both herein incorporated by reference. Abrasives are those compounds used in abrading grinding and polishing teeth Typical dentally acceptable abrasives include insoluble calcium salts, alumina, silica synthetic resins and mixtures thereof. U.S. Patent 4.623.536 discloses sodium bicar bonate, baking soda, as a mild abrasive and is herein incorporated by reference. Other compounds useful as abrasives are described in U.S. Patent 5.176.901 herei incorporated by reference. Pharmaceutical Agents The pharmaceutical actives of the present invention may be selected from among the various groups of chemical compounds or materials suitable for oral ad¬ ministration and having a pharmacological action. These pharmaceutically active compounds or materials should be compatible with the other essential ingredients and compatible in combination with other included active materials or compounds. The pharmaceutically active compounds or materials are present at a level from about 0.01% to about 75%, preferably from about 0.1% to about 50%, more preferably from about 1.0% to about 25% and most preferably from about 1.0% to about 10%. The pharmaceutically active materials or compounds may include, but are not limited to: bronchodilators, anorexiants, antihistamines, nutritional supplements (such as vi¬ tamins, minerals, fatty acids, amino acids, and the like), laxatives, analgesics, antac¬ ids, H2~receptor antagonists, antidiarrheals, decongestants, antitussives, antinause- ants, antibacterials, antifungals, antivirals, expectorants, anti-inflammatory agents, antipyretics vitamins and pharmaceutically acceptable salts and mixtures thereof The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases including inorganic bases and organic bases. Salts derived from inorganic bases include sodium, potassium, lithium, am¬ monia, calcium, magnesium, ferrous, zinc, manganous, aluminum, ferric, manganic salts and the like. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, tertiary and quaternary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as triethylamine, tripropylamine, 2-dimethylaminoethanol, 2- diethylaminoethanol, lysine, arginine, histidine, caffeine, procaine, N-ethylpiperidine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglycamine, theo- bromine, purines, piperazine, piperidine, polyamine resins and the like. Examples of useful decongestants include pseudoephedrine, phenylpro- panolamine, phenylephrine and ephedrine, their pharmaceutically acceptable salts, and mixtures thereof. Examples of useful antitussives include dextromethorphan, chlopedianol, car- betapentane, caramiphen, noscapine, diphenhydramine, codeine, hydrocodone, hy- dromorphone, their pharmaceutically acceptable salts, and mixtures thereof. Examples of useful expectorants (also known as mucorytic agents) include; glyceryt guaiacolate, terpin hydrate, ammonium chloride, N-acetyicysteine, and am- broxol, their pharmaceutically acceptable salts, and mixtures thereof. Examples of useful analgesics include; morphine, codeine, meperidine, penta- zocine, propoxyphene, acetaminophen, allopurinol, acetylsalicylic acid, choline salicyiate, ketoprofen, magnesium silicate, salsalate, fenoprofen, ibuprofen, in- domethacin, naproxen, and many others and their pharmaceutically acceptable salts and mixtures thereof. Analgesics, decongestants, expectorants and antitussives, as well as their ac¬ ceptable dosage ranges are described in U.S. Patent 4.783.465 to Sunshine et al., is¬ sued November 8, 1988, and U.S. Patent 4.619.934 to Sunshine et al., issued Octo¬ ber 28, 1986, which are incorporated by reference herein. Examples of useful antihistamines include; brompheniramine, chlor- pheriiramine, clemastine, dexchloφheniramine, diphenhydramine, doxylamine, pro- methazine, terfenadine, triprolidine and many others and their pharmaceutically ac¬ ceptable salts and mixtures thereof. Examples of useful gastrointestinal agents include; anticholinergics, including atropine, clidinium and dicyclomine; antacids, including aluminum hydroxide, bismuth subsalicylate, calcium carbonate and magaldrate; H2~receptor antagonists including: cimetidine, famotidine, nizatidine and ranitidine; laxatives, including: phenolphthalein and casanthrol; and antidiarrheals including: diphenoxylate and loperamide. Further examples of suitable analgesics, decongestants, antitussives, expecto¬ rants and antihistamines as well as bronchodilators, anorexiants, laxatives, antiemet- ics, aπtibacterials, antimicrobials, antifungals, anti-inflammatory agents, antivirals, antipyretics, nutritional supplements, anticholinergics, antacids, H2-receptor antago¬ nists, antidiarrheals and other miscellaneous gastrointestinal compounds and their ac¬ ceptable dosage ranges are described in Remington's Pharmaceutical Sciences, pp. 734-789, 791-799, 861-868, 907-945, 875-888, 1002-1034, 1098-1121, 1124-1131, 1173-1224, 1232-1241, (Alfonso RGennaro, editor) (18th ed. 1990), herein incor¬ porated by reference. Solvents or Solvent System Another essential ingredient of the composition of the present invention is a solvent or solvent system such as those described in U.S. Patent 5,141,961, August 25, 1992 to Coapman, herein incorporated by reference. The solvent(s), which constitute the bulk of the present composition act as a carrier for the flavoring oils. The solvent or solvent system solubilizes the flavoring oils in the concentrate and aids in dispersing, upon dilution with added water, all oil soluble components of the concentrated formulation thereby forming a uniformly dispersed mixture. The solvents most preferred for use in the present invention are: propylene glycol and polyethylene glycols or mixtures thereof. Propylene glycol and polyethylene glycols being most preferred. Propylene glycol is well known in the art and available from any of a number of suppliers. Propylene glycol is miscible in all proportions with water and also has the ability to dissolve the flavoring agent(s) of the present invention. Propylene glycol suitable for use in the present invention is obtainable from any number of sources such as Dow Chemical. Polyethylene glycols are also well known in the art and lower molecular weight species possess characteristics similar to propylene glycol. Polyethylene glycols suitable for use in the present invention are the polyethylene glycols having an average molecular weight of less than or equal to 600, such as PEG 300 "Carbowax" supplied by Union Carbide. Solvents comprise from about 30% to about 85%, preferably from about 35% to about 75% and most preferably from about 45% to about 60% of the concentrated form of the mouthrinse. Water Water is present in the concentrated composition of the present invention. Water comprises from about 10% to about 40%, preferably from about 18% to about 30% and most preferably from about 22% to about 26% of the oral compositions described herein. These amounts of water include the free water which is added, plus that amount which is introduced with other materials such as with sorbitol. The water, used in the present invention should preferably be deionized, distilled, free of organic impurities and bacteria and substantially free of metal ions. Pharmaceutical Carriers The compositions in which the present composition finds application are prin¬ cipally topical. These topical compositions include not only compositions such as dentifrices, mouthwashes, and gargles, but also compositions applied to, or which, in normal usage, come in contact with other internal mucous membranes of the body, such as those of the nose, mouth, or throat, regardless of whether that application is direct or indirect or via inhalation. These compositions find further applicability to the external surfaces of the human body - whether for medical or other reasons - as, for example, perfumes or powders as well as other skin care compositions, such as lotions, liniments, oils and ointments. Also included within the compositions of the present invention are articles such as cleansing tissues and toothpicks impregnated or coated with the active cooling compound. In formulating the compositions of the present invention, the ethanol imitating composition will usually be incorporated into a carrier which may be completely inert or contain other active ingredients. A wide variety of carriers may be used, depend- ing upon the end use of the composition, such carriers including solids, liquids, emulsions, foams and gels. Typical carriers include aqueous solutions; oils and fats such as hydrocarbon oils, fatty acid esters, long chain alcohols and silicone oils; finely divided solids such as starch or talc; cellulosic materials such as paper tissue; low- boiling hydrocarbons and halohydrocarbons used as aerosol propellants; gums and natural or synthetic resins. The following illustrates the range of compositions into which the present composition can be incorporated: 1. Oral hygiene compositions including mouthwashes, toothpastes, tooth- powders, prophylaxis pastes, lozenges, and gums providing antiplaque, antibacterial, antitartar, and/or abrasive activity. 2. Topical skin care compositions including after shave lotions, shaving soaps, creams and foams, water, deodorants and antiperspirants, "solid colognes", soaps, bath oils and salts, shampoos, hair oils, talcum powders, face creams, hand creams, sunburn lotions, cleansing tissues, toothpicks, hair tonics, eyedrops. 3. Medicaments including antiseptic ointments, liniments, lotions, decon¬ gestants, counter-irritants, cough mixtures, throat lozenges, antacid and indigestion preparations, oral analgesics, allergy products. 4. Miscellaneous compositions such as water soluble adhesive composi- tions for envelopes, postage stamps, adhesive labels etc. Particular preparations according to the invention are discussed in more detail below. Oral Hygiene Compositions: Because of the cooling, tingling and biting sensations imparted to the mouth, the present composition is particulariy useful in oral care products at a level of from about 0.35% to about 1.0%. Suitable oral care products would be those products including mouthwashes, tooth pastes, toothpowders, prophylaxis pastes, lozenges, and gums providing antiplaque antibacterial, antitartar, and/or abrasive activity. Topical skin Care Compositions:: Because of the ethanol imitating sensations imparted to the skin, a major utilit of the present invention will be in a wide range of skin care preparations and articles The particular preparations dis iyrd below are to be taken as exemplary. These compositions are especially useful in shaving lotions, water etc, whe the compounds are in aqueous solutions, such solutions will usually also contai perfumes or mud antiseptics or both. Another field of utility will be in soaps, shampoos, bath oils etc. where th compounds will be used in combination with an oil or fat or a natural or syntheti surfactant e.g. a fatty acid salt or a lauryl sulphate salt, the composition usually als containing an essential oil or perfume. The range of soap compositions WLQ includ soaps of all kinds e.g. skin care soaps, shaving soaps, shaving foams etc. A further class of skin care compositions into which the compounds may b incorporated includes cosmetic creams and emollients, such creams and emollients usually comprising a base emulsion and optionally a range of ingredients such as wax, preservative, perfume, antiseptics, astringents, pigments etc. Also included within this class are lipstick compositions, such compositions usually comprising an oil and wax base into which the compounds can be incorporated along with the conventional ingredients, i.e. pigments, perfumes etc. Once again the formulation of such compositions is conventional. Medicaments: In addition to the present composition's cooling, tingling and biting effect on the mucous membranes of the mouth, it produces similar effects on the skin, throat, nose and gastrointestinal tract, making t useful in combination with a variety o pharmaceutical actives. These compositions may take the form of oral, nasal, throat spray and/or topical pharmaceutical compositions. Certain compositions of this invention are illustrated by the following non- limiting examples. These examples are strictly given for illustration purposes. EXAMPLES The following examples further describe and demonstrate embodiments whhin the scope of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present inven- tion, as many variations are possible without departing from the spirit and scope of the invention. EXAMPLE I A mouthwash composition is made by combining the following components. Ingredients W/W propylene glycol 10.0000 flavor 0.1750 poh/sorbate-80 0.0500 po_oxamer-407 0.2000 2-phenoxyethanol 0.5000 3-1-menthoxypropane 1,2-diol 1 0.0555 N-ethvl-p-meπthane-3-carboxamide 2 0.0225 N,2,3-t__metlτyl-2- opropy-buta-__mid 3 0.0125 ethyl acetate 0.0050 sodium saccharin 0.0540 sodium benzoate 0.0540 glycerin, USP 10.0000 benzoic acid 0.0045 blue dye No.1, 1.00% solution 0.0300 yellow dye No.5, 1.00% solution 0.0300 purified water q.s. to 100 1 Available as TK-10 supplied by Takasago Perfumery Co. 2 Available as WS-3 supplied by Steriing Orgamcs. 3 Available as WS-23 supplied by Wilkinson Sword Limited. In a stainless steel or glass mixing tank containing the quantity of solvent, se ¬ quentially add the following ingredients dissolving each with agitation: alkoxy or glycol ether, ethyl acetate, cooling agent, antibacterial, humectant(s), purified water, and dye. EXAMPLE II An aftershave composition is made by combining the following components using conventional mixing technology as described in Example I. Ingredients W/V% Non-alcohol Fragrance 1.500 Hexylene G-ycoi 37.500 2-phenoxyethanol 3.360 Ethyl acetate 0.032 3-1-meπthσxypropaιιe 1,2-diol 0.376 N-ethyl-p-menthane-3-carboxamide 0.152 N,2,3-trimethyi-2-isopropyibutanamid 0.080 Water Q.S. to 100% EXAMPLE m A pharmaceutical composition is made by combining the followin components using conventional mixing technology as described in Example L Ingredients W/V% Acetaminophen 3.33333 Iλ>xyiamtne Sucάnate 0.04166 Pseudoephedrine HC1 0.20000 Dextromethorphan HBr 0.10000 Sodium Citrate, Hydrous 1.00000 Sugar Liquid #1 65.00000 Sodium Saccharin 0.07000 Citric Acid, Anhydrous 0.22856 Glycerin 5.00000 Propylene Glycol 15.00000 Polyethylene Glycol 400 5.00000 Anethol 0.01483 Green Shade CSL- 15689 0.00500 2-phenoxyethanol 0.33600 Ethyl acetate 0.00320 3-1-menthoxypropane 1,2-diol 0.03760 N-ethyl-p-menthane-3-carboxamide 0.01520 N,2,3-tri_nethyl-2-isopropylbutanamid 0.00800 Water Q.S. to 100%

Claims: What is Claimed is: 1. A composition which provides physiologic sensations similar to ethanol and characterized in that it comprises: a) an alkoxy or glycol ether, preferably selected from among the group consisting of 2-phenoxyethanol, 2-butoxyethanol, 2-ethoxyethanol, or 2-phenoxypropanol, more preferably 2-phenoxyethanol; and b) ethyl acetate; in a ratio of from 50 to 1 to 1000 to 1. 2. A composition according to Claim 1 which additionally comprises a cooling agent, preferably selected from the group consisting of: 3-1-methoxypropane 1,2-diol, N-ethyl-p-methane-3-carboxamides, and acyclic carbamides and mixtures thereof, in a ratio of alkoxy or glycol ether: cooling agent of from 2 to 1 to 1000 to 1, respectively. 3. A composition according to any one of the preceding Claims which additionally comprises an oral carrier. 4. A composition according to any one of the preceding Claims which additionally comprises a carrier selected from the group consisting of mouthwashes, toothpastes, toothpowders, prophylaxis pastes, lozenges, and gums which additionally comprises an active ingredient having antiplaque activity. 5. A mouthrinse carrier according to any one of the preceding Claims which additionally comprises an active ingredient having antibacterial activity. 6. A mouthrinse carrier according to any one of the preceding Claims which additionally comprises an active ingredient having antitartar activity. 7. A mouthrinse carrier according to any one of the preceding Claims which additionally comprises a dentally acceptable abrasive. 8. A composition according to any one of the preceding Claims which additionally comprises a pharmaceutical carrier. 9. A pharmaceutical composition according to any one of the preceding Claims which additionally comprises pharmaceutically active ingredients selected from the group consisting of: an antitussive; an antinauseant; a nutritional supplement; a laxative; an appetite suppressant; an analgesic; an antiasthmatic; an antihistamine; a decongestant; an expectorant; an antacid; an antidiarrheal, a H2-Receptor antagonist an mixtures thereof. 10. A composition according to any one of the preceding Claims which additionally comprises a topical carrier, preferably in the form of a skin care composition.

Inventors: HALL WILLIAM GERALD, MCLAUGHLIN KEVIN THOMAS, HALL, WILLIAM, GERALD, MCLAUGHLIN, KEVIN, THOMAS
Applicants: PROCTER & GAMBLE, THE PROCTER & GAMBLE COMPANY
Application year: 1994
Main classification: A61K7
IPC codes: A61K8, A61K9, A61Q11, A61Q19